Different Pathogeneses May Cause Dementia in Older, Younger Patients With PD

Older patients with Parkinson disease (PD) were found to have a higher incidence of dementia compared with younger patients. However, the difference may have to do with different pathologies causing dementia in older and younger patients.

Older patients with Parkinson disease (PD) were found to have a higher incidence of dementia, likely due to a higher incidence of coexisting pathologies, suggesting that different pathogenesis and pathologies cause dementia in younger and older patients with PD, according to a recent study.

The nationwide, population-based, retrospective cohort study from Taiwan, published in Frontiers in Neurology, is the first to observe dementia associated with newly diagnosed PD in younger age stratifications.

Dementia is among the most disabling nonmotor symptoms that manifest in patients with PD, but it has largely been ignored. Because of medication improvements, patients with PD have longer life expectancies and providers can observe the whole picture in regard to the disease's cognitive changes.

Cortical or limbic Lewy-related pathology (LP), coincidence Alzheimer-type pathology, and subcortical pathology are the 3 types of pathology thought to cause PD-related dementia, potentially resulting in the impaired projection of dopamine, noradrenaline, serotonin, and acetylcholine neurons to the neocortex.

The investigators selected 760 patients with a new diagnosis of PD and 3034 control subjects from Taiwan’s National Health Insurance Research Database (NHIRD) from January 2001 to December 2005. The mean (SD) age of the entire cohort was 60.8 (17.6) years, and 53.0% were male. By comorbidities, 30.4% of the cohort had hypertension, 13.3% had diabetes, 11.0% had hyperlipidemia, 1.6% had chronic kidney disease (CKD), and 12.0% had ischemic heart disease (IHD).

The overall incidence of dementia was 17.5 per 1000 person-years in the PD group and 5.7 per 1000 person-years in the control group. When stratifying by age, the investigators found that older patients had a higher incidence of dementia in the PD and control groups, especially those over the age of 70 years (39.7 and 13.1 per 1,000 person-years, respectively).

Male and female patients had a higher incidence of dementia in the PD group, and female patients had higher dementia incidence than male patients in both the PD and control groups ( 19.6 vs 15.6 per 1000 person-years and 6.1 vs 5.3 per 1000 person-years, respectively).

After adjusting for hypertension, type 2 diabetes, hyperlipidemia, CKD, and IHD, the PD group had a significantly higher overall risk of developing dementia compared with controls (adjusted HR, 3.23; 95% CI, 2.47-4.22; P < .001). A significantly higher risk of developing dementia was also observed in the PD group in each age stratification.

Although the dementia incidence rate was low (2.0 per 1000 person-years) in patients with PD younger than 60 years, the risk was 6.55 times greater in the young age stratification compared with the control group.

The investigators said that older age, female sex, and PD were considered important factors associated with higher risk of dementia. Hypertension, type 2 diabetes, hyperlipidemia, CKD, and IHD were not found to have a significant effect on the risk of dementia. A significantly lower dementia-free survival rate in patients with PD compared with the participants who did not have PD was also observed during the follow-up period (P < .001).

“The cortical [Lewy-related pathology] deposition and co-pathologies of the old-onset PD subtype may lead to faster clinical progression and a higher incidence of cognitive impairment than the early onset PD subtype,” the investigators wrote.

A major limitation of the study was that the dataset did not contain information regarding severity of motor or nonmotor symptoms, relevant genetic factors or family history of PD, educational level, clinical dominant types of motor symptoms, and presence of mild cognitive impairment. Other limitations included potential coding errors associated with the NHIRD and surveillance bias.


Chang TY, Yang CP, Chen YH, Lin CH, Chang MH. Age-stratified risk of dementia in Parkinson’s disease: A nationwide, population-based, retrospective cohort study in Taiwan. Front Neurol. December 24, 2021;12:748096. doi:10.3389/fneur.2021.748096

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